Resting T cells do not express high-affinity IL-2 receptors, but receptors are rapidly expressed on T cells after activation with antigen or mitogen. There are two classes of IL-2 receptors that differ in their affinity for IL-2, including one with a very high affinity and the other with a much lower affinity. ln a major development, a novel 75-kDa non-Tac IL-2 binding peptide was identified. Cell lines bearing either the 55-kDa Tac or the p75 peptide alone manifested low affinity IL-2 binding, whereas cell lines bearing both peptides manifested both high and low affinity receptors. Fusion of cell membranes from low-affinity IL-2 binding cells bearing the Tac peptide alone with membranes from a cell line bearing the p75 peptide alone generated hybrid membranes bearing high-affinity receptors. These observations suggested a multichain model for the high-affinity IL-2 receptor in which both the p55 Tac and the p75 IL-2 binding peptides are associated in a receptor complex. Essentially all T cell functions require that the T cell be activated and express both the 55-kDa Tac peptide as well as the novel 75-kDa IL-2 binding peptide. The pattern with lymphokine activated killer (LAK) cells and natural killer (NK) cells is quite different. Over the past year, it was shown that such LAK and NK precursor cells, as well as different types of leukemia of large granular lymphocytes with NK activity, express the p75 but not the 55-kDa IL2 binding peptide. Evidence has been presented suggesting that a third 95-110 kd peptide is an associated participant in the multichain IL-2 receptor. In contrast to resting cells, certain leukemic T cells, T cells involved in autoimmune disorders and in allograft rejection express the Tac peptide. To exploit this differential expression, clinical trials of patients with Tac positive adult T cell leukemia have been initiated using unmodified anti-Tac toxin conjugated and isotope chelated anti-Tac.